Dolutegravir is chemically known as (4R,12aS)-9-{[(2,4-difluorophenyl)methyl] carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino [2,1-b][1,3]oxazin-7-olate, having the following Formula I:

Dolutegravir (DTG, GSK1349572) is an integrase inhibitor being developed for the treatment of human immunodeficiency virus (HIV)-1 infection. Sodium salt of dolutegravir was recently approved by FDA and marketed under the brand name of TIVICAY by ViiV Healthcare and manufactured by GlaxoSmithKline. TIVICAY is administered orally as a tablet of 50 mg strength.
Tivicay is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Dolutegravir and a process for its preparation was first described in U.S. Pat. No. 8,129,385 and the disclosed process of dolutegravir involves 16 steps which is schematically represented as follows:
U.S. Pat. No. 8,217,034 (“the '034 patent”) discloses the preparation of Dolutegravir. The process disclosed in the '034 patent is schematically represented as follows:

U.S. Pat. No. 8,552,187 (“the '187 patent”) discloses the preparation of Dolutegravir intermediate. The process disclosed in the '187 patent is schematically represented as follows:

PCT Publication No. WO 2011/119566 (“the '566 publication”) discloses the preparation of Dolutegravir. The process disclosed in the '566 publication is schematically represented as follows:

PCT Publication No. WO 2012/018065 (“the '065 publication”) discloses the different preparation methods to prepare Dolutegravir. The preparation methods disclosed in the '065 publication is schematically represented as follows:
Preparation Method 1:
Preparation Method 2:
Preparation Method 3:

Indian patent publication 1361/CHE/2013 discloses a process for the preparation of dolutegravir, which involves the reaction 5-methoxy-6-(methoxycarbonyl)-4-oxo-1(2-oxoethyl)-1,4-dihydropyridine-3-carboxylic acid with tartarate salt of (R)-3-amino-1-butanol in presence of sodium acetate in acetonitrile to provide (4R, 12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro2H-pyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylicacid, which on condensation with 2,4-difluorobenzylamine in presence of pivaloyl chloride, triethylamine in methylene chloride to provide (4R, 12aS)-N-(2,4-difluorobenzyl)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino [2,1-b][1,3]oxazine-9-carboxamide, which on reaction with lithium bromide in isopropyl alcohol provides dolutegravir.
PCT Publication No. WO 2015001572 (“the '572 publication”) discloses the two different method for the preparation of dolutegravir intermediate i.e., methyl 3-(benzyloxy)-5-(2,4-difluorobenzylcarbamoyl)-4-oxo-1-(2-oxoethyl)-1,4-dihydropyiridine-2-carboxylate. The preparation methods disclosed in the '572 publication is schematically represented as follows:
Method-1:
Method 2:

Dolutegravir is one of the important drug which is recently approved and available in the market for the treatment of human immunodeficiency virus (HIV)-1 infection. Hence it is advantageous to have alternate process for its preparation.
The main objective of the present invention is to provide an alternate process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof.